Inherited variations in proteins of the nervous system have been hypothesized to underlie differences in mood, behavior, neurophysiology, neuroanatomy and response to drugs in normal individuals, as well as in neurologic and psychiatric patients. These studies will focus on the two neural proteins, catechol-0-methyltransferase (COMT) and Beta-nerve growth factor (Beta-NGF) which are amenable to biochemical and genetic analysis for which inherited variations in function are thought to occur in humans. For COMT, the number, location and structure of human genes coding for multiple forms of this enzyme will be assessed. Further, it will be established whether inherited variations in COMT activity, measured in red blood cell lysates and thought to affect drug metabolism, are caused by allelic variations in structural gene locus for this enzyme. This will elucidate the relationship between multiple forms of COMT, and the molecular basis of normal variations in activity. The role of Beta-NGF in the inherited neurologic disease, familial dysautonomia, will be assessed by establishing whether or not specific alleles for the structural gene are co-inherited with the disease state in affected families. Further, a source of authentic human Beta-NGF will be sought using antibodies prepared against recombinant human "Beta-NGF" and a cloned DNA probe for the human Beta-NGF mRNA. By characterizing the authentic form of this human protein it will be possible to investigate its role in other neurologic diseases. Methods to be employed include protein biochemistry, e.g. gel electrophoresis, peptide mapping, microsequencing; immunological techniques, e.g. immunoblotting, immune precipitation, immunoaffinity adsorption of polysomes, radioimmunoassays; molecular biologic techniques, e.g. in vitro translation of mRNA, cDNA cloning in expression and non-expression plasmids, restriction endonuclease mapping, nucleotide sequencing, Southern and Northern blotting; and cell culture procedures, e.g. transformation of lymphocytes, analysis of somatic cell hybrids, radioreceptor assays.